Regulatory T cells in the "missing link" between dysbiosis and allergic diseases

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K22526
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 49:Pathology, infection/immunology, and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Hori Shohei 東京大学, 大学院薬学系研究科(薬学部), 教授 (50392113)
• Project Period (FY): 2019-06-28 – 2022-03-31
• Keywords: アレルギー疾患 / 制御性T細胞 / dysbiosis

Outline of Final Research Achievements

We have previously reported that mice bearing the Foxp3 A384T mutation, which has been identified in patients with the autoimmune disease IPEX, spontaneously develop chronic allergic responses in mucosal tissues such as the lung and colon due to impaired accumulation of immune suppressive regulatory T cells in these sites. In the present study, we aimed to address whether the normal microbiota contributes to the chronic allergic responses by raising Foxp3 A384T mutant mice under germ-free conditions. We found that the microbiota elicited allergic responses in the colon, but not in the lung, of Foxp3 A384T mutant mice by stimulating type 2 helper T cells.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

アレルギー疾患を促進する環境要因として常在細菌叢の構成異常が注目されている。そのメカニズムとして制御性T細胞の関与が示唆されているが、これまでアレルギー反応制御における常在細菌と制御性T細胞の関連と相互作用メカニズムはよくわかっていない。本研究は、Foxp3 A384T変異マウスをモデルとして、制御性T細胞機能異常と常在細菌が相乗的に大腸においてアレルギー反応を惹起する（すなわち、制御性T細胞が常在細菌に対するアレルギー反応を抑制している）ことを明らかにした点で学術的な意義がある。